Antibacterial detergent compositions containing phenylbismuth bis(2-pyridinethiol 1-oxide)

ABSTRACT

Phenylbismuth bis(2-pyridinethiol 1-oxide), a new antibacterial and antifungal compound, and compositions containing same.

Unlted States Patent 11 1 1111 3,890,242 Curry 5] June 17, 1975 1ANTIBACTERIAL DETERGENT [51] Int. Cl Cl 1d 3/48 COMPOSITIONS CONTAINING[58] Field of Search 252/D1G. 16, 206, 207, PHI-INYLBISMUTHBIS(2-PYRIDINETHIOL lG- 13, DIG. 5; 2 /245 l-OXIDE) [75] Inventor: JohnDowning Curry, Oxford, Ohio [56] References Cited [73] Assignee: Procter& Gamble Company, UNITED STATES PATENTS Cincinnati Ohio 3,239,411 3/1966Lecbnck 260/270 R 3,281,366 10/1966 Judge et a1 252/106 X [22] Filed:Mar. 30, 1973 3,321,480 5/1967 Schroder ct a1.... 260/270 R 3,583,9996/1971 Damico 260/270 R [211 PP N04 346,396 3,835,057 9/1974 Cheng eta1.... 252/107 Related US. Application Data [60] Division of Ser. No.218,584, Jan. 17, 1972, Pat. No. W Padgett 3,753,990, which is acontinuation-in-part of Ser. No. Assistant EXammer E' Mlllcr 98,086,Dec. 14, 1970, abandoned, Attorney, Agent, or Firm--Ronald L. Hemmgway;

Robert B. Aylor; Richard C. Witte [30] Foreign Application Priority DataApr. 4, 1972 Netherlands 7204437 [57] ABSTRACT Apr. 7, 1972 France72.12388 phenylbismuth bis(2 pyridinethi0l l oxide) a new 1972 Germany"22/1672 antibacterial and antifungal compound, and composi- Apr. 10,1972 Sweden 4611/72 tions containing Same Apr. 13, 1972 United Kingdom17088/72 6 Claims, N0 Drawings [52] US. Cl. 252/107; 252/106; 252/DIG.5;

252/D1G. 13; 252/D1G. 16; 424/245 ANTIBACTERIAL DETERGENT COMPOSITIONSCONTAINING PI-IENYLBISMUTII BlS(2-PYRIDINETHIOL I-OXIDE) CROSS-REFERENCETO RELATED APPLICATIONS This is a divisional application of my copcndingapplication Ser. No. 218,584, filed Jan. 17, 1972. for PHENYLBISMUTHBIS(2-PYRID1NETHIOL 1- OXIDE AND COMPOSITIONS CONTAINING SAME, now U.S.Pat. No. 3,753,990, which is turn is a continuation-in-part of myapplication Ser. No. 98,086, filed Dec. 14, 1970, for PHENYLBISMUTHDI(PYRIDINETHIONE-N-OXIDE) AND COMPOSI- TIONS CONTAINING SAME," nowabandoned.

BACKGROUND OF THE INVENTION 1. Field of the Invention The presentinvention relates to a new compound, phenylbismuth bis(2-pyridinethioll-oxide), which can be formed by the reaction between sodium 2-pyridinethiol l-oxide and diphenylbismuth acetate. This invention alsorelates to the use of this compound, which is highly effective against abroad spectrum of bacteria as well as yeast and fungal species,especially when used on the skin, where the compound is fairlysubstantive, and to compositions, including detergent compositions,containing said compound.

2. Prior Art Leebricks U.S. Pat. No. 3,239,411, issued Mar. 8, 1966;Gross U.S. Pat. No. 3,197,314 issued July 27, I965; Leebricks BelgianPat. No. 1.426,l18; and American Cyanamids British Pat. No. 1,003,695teach that various organo-bismuth compounds, including diphenylbismuthacetate, are effective antibacterial and antifungal agents for useagainst a wide variety of gram positive and gram-negative organisms.Similarly, the sodium salt of 2-pyridinethiol l-oxide is known. See,e.g., British Pat. No. 761,171, and U.S. Pat. Nos. 2,742,393, and2,742,476. Schroder et al.s U.S. Pat. No. 3,321,480 teaches triphenyltin (2-pyridinethione) [triphenyl tin (Z-pyridinethiol 1-oxide)].

SUMMARY OF THE INVENTION Phenylbismuth bis(2-pyridinethiol l-oxide) hasthe formula:

om G9) Compositions containing phenylbismuth bis(2- pyridinethioll-oxide) have excellent broad-spectrum antibacterial and anti-fungalaction.

Phenylbismuth bis(2-pyridinethiol l-oxide), hereinafter referred to asPBDP, is a yellow powder having a melting point at about 215-2l 8. It isgenerally insoluble in most common solvents, but is soluble to theextent of about 1% in dimethylsulfoxide, dimethylformamide ordimethylacetamide. The dry solid PBDP is stable and the PBDP appearsstable in the presence of soap solutions (pl-I 9-10) and hydrochloricacid (pH Phenylbismuth bis(2-pyridinethiol I-oxide) has been shown toexhibit antibacterial and antifungal effectiveness against, e.g.,Gram-positive organisms such as: Brr'i'ibacrerium ammoniagenes,Erysipelotlu'ix [n.rizliosa, Laclulmcillus leiclzmanni, Bacillussubtilus. (lostrizlizmz perfiingens, .S'raplz -'l0c0ccus aureas,Staplrvlvcoct'as' epi- (lermidis, Sart'ina lurca,Streptococcusfavc'alis. ('orynvlmclerlum acnar. Axilla diplillzeroizlNo. 16, Oral Sm'plococcas No. 125, Mycobacterium pltlel, Mycohacu'riumsmeqmatis, and Mymbacterium hulnei; Gram-negativc organisms such as:Alkaligenes faetalis, Salmmwlla 1yplmsa,. Shigella flarncri, Mimapolymorpha, Hera/lea vaginicola, Hemoplzilus gallinarum. Proteusmirahilis, Vibrio nzctscllniltovii, Neissc'ria flai'esc'ens, Escherichiacoli, Pscmlomonas ueruginosa, Scrralia martext'cns. Klebsiellapneumoniae, and Enterobacter aerogencs; and Fungi (including yeasts anddermatophytes) such as: Aspergillus niger, Mycrosporum gypseum,Triclmplrrton rubrum, Ticlwphyton interdigilale, Sacclzaromyces(erevisiae, Candida albicans, and Pityrosporum ova/e.

Because of the extremely broad antibacterial and antifungaleffectiveness of PBDP it is desirably used as a component of surgicalscrub products, bar soaps, shampoos, oral products (e.g., toothpastes,mouthwashes, etc.), first aid sprays. foot powder, deodorants (especially underarm deodorants), first aid cream, toilet bowl cleaners, hardsurface cleaners, detergents, paints, cosmetics, spermicides, burndressings, animal feeds, wood preservatives, mildewcides, germicides,algacides, fungicides, medicines, packing preservatives, etc. Inextremely small amounts, e.g., 10 ppm., the PBDP will inhibit the growthof a broad variety of organisms. When the PBDP is incorporated in largeramounts, the compositions can be used to destroy organisms, as required.For example, in medicine, both for humans and veterinary medicine, thePBDP can be used to treat a variety of diseases and/or organismsincluding acne, leprosy, psoriasis, warts, intestinal parasites,dandruff, pseudomonas or coli bacteria, fungus (e.g., athletes foot),vaginal infections, etc. Compositions containing PBDP can be used totreat tissue either to prevent infections or to cure infections.

PBDP is not inactivated by urine or hair oil, but its activity issomewhat diminished by human serum or human red blood cell lysate. Itsactivity is somewhat greater in acid to neutral media against S. aureusand E. coli. PBDP is substantive to-tooth enamel and cellulose. Thus,PBDP can be used to prevent the growth of plaque in the mouth and can beused against gingivitis. Also, it can be used on bandages, diapers, andsanitary napkins to prevent infections, diaper rash, odor, etc. PBDP canalso be used as a slimicide ancl preservative for paper and wood.

PREPARATION OF Pl-IENYLBISMUTH BIS(2-PYRIDINETHIOL l-OXIDE)Phenylbismuth bis(2-pyridinethiol l-oxide) can be prepared by reactingdiphenylbismuth acetate with sodium 2-pyridinethiol l-oxide in a 1:1molar ratio in a solvent such as dimethyl formamide. The compound, ayellow precipitate, can then be filtered and purified as exemplifiedhereinafter in Example 1. Other reactions to form phenylbismuthbis(2-pyridinethiol I-oxide) include the reaction of sodium, potassium,ammonium, or lithium 2-pyridinethiol l-oxide or any other saltcontaining a loosely held cation with a phenylbismuth dihalide (e.g., achloride, bromide, or iodide).

COMPOSITIONS CONTAINING PH ENYLBlSMUTl-l BlS(2-PYRIDINETHIOL l-OXIDE)Phenylbismuth bis(2-pyridinethiol l-oxide) can be used in aqueous and/ornon-aqueous solvents to provide antibacterial action. Preferably. thecompositions will contain from about 0.2 to about 3% phenylbismuthbis(2-pyridinethiol l-oxide), most preferably from about 1 to about 2%.Desirable compositions are those containing soap and non-soap syntheticdetergent compounds. Preferably, the synthetic detergent compounds arecationic, amphoteric, or nonionic.

The term soap" as used herein is meant to designate alkali metal soapssuch as the sodium and potassium salts of the higher fatty acids ofnaturally occurring plant or animal esters, e.g., palm oil, coconut oil,babassu oil, soybean oil, castor oil, tallow, whale and fish oils,grease and lard and mixtures thereof. Sodium and potassium soaps can bemade by direct saponification of the fats and oils or by theneutralization of the fatty acids which are prepared in a separatemanufacturing process. Examples of suitable soaps are the sodium,potassium, ammonium and alkylolammonium salts of higher fatty acids {C CParticularly useful are the sodium and potassium salts of the mixturesof fatty acids derived from coconut oil and tallow, i.e., sodium orpotassium tallow and coconut soap.

Anionic synthetic detergents which can be used with the antibacterial,antifungal, and antiyeast compound of the present invention can bebroadly defined as the watersoluble salts, including the alkali metal,ammonium and substituted ammonium salts, or organic sulfuric reactionproducts having in their molecular structure an alkyl radical containingfrom about 8 to about 22 carbon atoms and a radical selected from thegroup consisting of sulfonic acid and sulfuric acid ester radicals.

Important examples of the synthetic detergents which can be used withthe compound of the present invention are the following: alkali metal(e.g., sodium and potassium), ammonium and substituted ammonium (e.g.,lower alkyl ammonium) salts of the following: alkyl sulfates, especiallythose obtained by sulfating the higher alcohols produced by reducing theglycerides of tallow or coconut oil; random paraffin sulfonates, inwhich the alkyl group contains from about 8 to about 22 carbon atoms,prepared by treating random paraffin hydrocarbons in sulfur dioxide andchlorine in the presence of light followed by treating with a base;branched or linear alkyl benzene sulfonates, in which the alkyl groupcontains from about 8 to about 18 carbon atoms, preferably from about 10to about 14 carbon atoms, especially those of the types described inU.S. Pat. Nos. 2,220,099, and 2,477,383; sodium alkyl glyceryl ethersulfonates, especially those ethers of the higher alcohols derived fromtallow and coconut oil; coconut oil fatty acid monoglyceride sulfatesand sulfonates; sulfuric acid esters of the reaction product of one moleof a higher fatty alcohol (e.g., tallow or coconut alcohols) and fromabout 1 to about 6, preferably about 3 moles of ethylene oxide; alkylphenol ethylene oxide ether sulfates with about 4 units of ethyleneoxide per molecule and in which the alkyl radicals contain about 9carbon atoms; the reaction product of fatty acids esterified withisethionic acid and neutralized with sodium hydroxide where, forexample, the fatty acids are derived from coconut oil; fatty acid amidesof the methyl taurine in which the fatty acids, for example, are derivedfrom coconut oil; sulfonated olefins of U.S. Pat. No. 3,332,880; andothers known in the art, a number being specifically set forth in U.S.Pat. Nos. 2,486,92l, 2,486,922 and 2,396,278.

The nonionic synthetic detergents which can be used with theantibacterial compound of the present invention may be broadly definedas compounds produced by the condensation of alkylene oxide groups(hydrophilic in nature) with an organic hydrophobic compound which maybe aliphatic or alkyl-aromatic in nature. The length of the hydrophilicor polyoxyalkylene radical which is condensed with any particularhydrophobic group can be readily adjusted to yield a watersolublecompound having the desired degree of balance between hydrophilic andhydrophobic elements.

For example, a well-known class of nonionic synthetic detergents is madeavailable on the market under the trade name of Pluronic. Thesecompounds are formed by condensing ethylene oxide with a hydrophobicbase formed by the condensation of propylene oxide with propyleneglycol. The hydrophobic portion of the molecule which, of course,exhibits water insolubility has a molecular weight of from about 1,500to about 1,800. The addition of polyoxyethylene radicals to thishydrophobic portion tends to increase the water solubility of themolecule as a whole and the liquid character of the products is retainedup to the point where polyoxyethylene content is about 50% of the totalweight of the condensation product.

Other suitable nonionic synthetic detergents include:

1. The polyethylene oxide condensates of alkyl phenols, e.g., thecondensation products of alkyl phenols having an alkyl group containingfrom about 6 to 12 carbon atoms in either a straight chain or branchedchain configuration, with ethylene oxide, the said ethylene oxide beingpresent in amounts equal to 10 to 60 moles of ethylene oxide per mole ofalkyl phenol. The alkyl substituent in such compounds may be derivedfrom polymerized propylene, diisobutylene, octane, or nonane, forexample.

2. Those derived from the condensation of ethylene oxide with theproduct resulting from the reaction of propylene oxide and ethylenediamine products which may be varied in composition depending upon.

the balance between the hydrophobic and hydrophilic elements which isdesired. For example, compounds containing from about 40 to aboutpolyoxyethylene by weight and having a molecular weight of from about5,000 to about 11,000 resulting from the reaction of ethylene oxidegroups with a hydrophobic base constituted of the reaction product ofethylene diamine and excess propylene oxide, said base having amolecular weight of the order of 2,500 to 3,000, are satisfactory.

3. The condensation product of aliphatic alcohols having from 8 to 18carbon atoms, in eitherstraight chain or branched chain configuration,with ethylene oxide, e.g., a coconut alcohol ethylene oxide condensatehaving from 10 to 30 moles of ethylene oxide per mole of coconutalcohol, the coconut alcohol fraction having from 10 to 14 carbon atoms.

4. Long chain tertiary amine oxides corresponding to the followinggeneral formula, R R R N 0, wherein R contains an alkyl, alkenyl ormonohydroxy alkyl radical of from about 8 to about 18 carbon atoms, from0 to about 10 ethylene oxide moieties, and from 0 to l glyceryl moiety,and R and R contain from 1 to about 3 carbon atoms and from 0 to about 1hydroxy group, e.g., methyl, ethyl, propyl, hydroxy ethyl, or hydroxypropyl radicals. The arrow in the formula is a conventionalrepresentation of a semi-polar bond. Examples of amine oxides suitablefor use in this invention include dimethyldodecylamine oxide,oleyldi(2-hydroxyethyl- ,)amine oxide, dimethyloctylamine oxide,dimethyldecylamine oxide, dimethyltetradecylamine oxide, 3,6-,9'trioxaheptadecyldiethylamine oxide, di(2-hydroxyethyl)tetradecylamineoxide, 2-dodecoxyethyldime thylamine oxide,3-dodecoxy-2-hydroxypropyldi(3- hydroxypropyl)amine oxide,dimethylhexadecylamine oxide.

5. Long chain tertiary phosphine oxides corresponding to the followinggeneral formula RR'R"P O, wherein R contains an alkyl, alkenyl ormonohydroxyalkyl radical ranging from 8 to 18 carbon atoms in chainlength, from 0 to about ethylene oxide moieties and from O to l glycerylmoiety and R and R are each alkyl or monohydroxyalkyl groups containingfrom 1 to 3 carbon atoms. The arrow in the formula is a conventionalrepresentation of a semipolar bond. Ex-

amples of suitable phosphine oxides are:

dodecyldimethylphosphine oxide, tetradecyldimethylphospine oxide,

'tetradecylmethylethylphosphine oxide,

3,6,9-trioxaoctadecyldimethylphosphine oxide, cetyldimethylphosphineoxide, 3-dodecoxy-2-hydroxypropyldi( 2-hydroxyethyl)- phosphine oxide,

stearyldimethylphosphine oxide, cetylethylpropylphosphine oxide,oleyldiethylphosphine oxide,

dodecylidiethylphosphine oxide,

tetradecyldiethylphosphine oxide,

dodecyldipropylphosphine oxide, dodecyldi(hydroxymethyl)phosphine oxide,dodecyldi(2"hydroxyethyl)phosphine oxide,tetradecylmethyl-2-hydroxypropylphosphine oxide, oleyldimethylphosphineoxide, 2-hydroxydodecyldimethylphosphine oxide.

6. Long chain dialkyl sulfoxides containing one short chain alkyl orhydroxy alkyl radical of l to about 3 carbon atoms (usually methyl) andone long hydrophobic chain which contains alkyl, alkenyl, hydroxy alkyl,or keto alkyl radicals containing from about 8 to about 20 carbon atoms,from O to about 10 ethylene oxide moieties and from 0 to 1 glycerylmoiety. Examples include:

octadecyl methyl sulfoxide,

Z-ketotridecyl methyl sulfoxide,

3,6,9-trioxaoctadecyl 2-hydroxyethyl sulfoxide,

dodecyl methyl sulfoxide,

oleyl 3-hydroxypropyl sulfoxide,

tetradecyl methyl sulfoxide,

3-methoxytridecyl methyl sulfoxide 3-hydroxytridecyl methyl sulfoxide,

3-hydroxy-4-dodecoxybutyl methyl sulfoxide.

The zwitterionic synthetic detergents useful with the antibacterialagent of the present invention can be broadly described as derivativesof aliphatic quaternary ammonium, phosphonium, and sulfonium compounds,in which the aliphatic radicals can be straight chain or branched. andwherein one of the aliphatic substituents contains from about 8 to 18carbon atoms and one contains an anionic water solubilizing group, e.g.,carboxy,

sulfonate, sulfate, phosphate, or phosphonate. A general formula forthese compounds is:

wherein R contains an alkyl, alkenyl, or hydroxy alkyl radical of fromabout 8 to about 18 carbon atoms, from 0 to about 10 ethylene oxidemoieties and from O to l glyceryl moiety; Y is selected from the groupconsisting of nitrogen, phosphorus, and sulfur atoms; R is an alkyl ormonohydroxyalkyl group containing 1 to about 3 carbon atoms; x is 1 whenY is a sulfur atom and 2 when Y is a nitrogen or phosphorus atom; R isan alkylene or hydroxyalkylene of from 1 to about 4 carbon atoms and Zis a radical selected from the group consisting of carboxylate,sulfonate, sulfate, phosphonate, and phosphate groups.

Examples include:

4-[N,N-di(2-hydroxyethyl)-N-octadecylammonio]- butane-l-carboxylate;5-[S-3-hydroxypropyl-S-hexadecylsulfonio]-3- hydroxypentanel -sulfate;

3-[P,P-diethyl-P-3,6,9-

trioxatetradecoxylphosphonio]-2-hydroxypropane- 1 -phosphate;3-[N,N-dipropyl-N-3-dodecoxy-2- hydroxypropylammonio]-propane- 1-phosphonate;

3-( N ,N-dimethyl-N-hexadecylammonio)propane l sulfonate;3-(N,N-dimethyl-N-hexadecylammonio)-2- hydroxypropanel -sulfonate;4-[N,N-di(2-hydroxyethyl)-N-(2- hydroxydodecyl)ammonio]-butanel-carboxylate; 3-[S-ethyl-S-(3-dodecoxy-2- hydroxypropyl )sulfonio-propane- 1 -phosphate', 3-[P,P-dimethyl-P-dodecylphosphonio]-propanelphosphonate; and

hexadecylammonio]2-hydroxypentanel -sulfate.

The amphoteric synthetic detergents useful in the present invention canbe broadly described as derivatives of aliphatic secondary and tertiaryamines in which the aliphatic radical can be straight chain or branchedand wherein one of the aliphatic substituents contains from about 8 toabout 18 carbon atoms and one contains an anionic water solubilizinggroup, e.g., carboxy, sulfonate, sulfate, phosphate, or phosphonate.Examples of compounds falling within this definition are sodium3-dodecylaminopropionate, sodium 3- dodecylaminopropane sulfonate,dodecyl-B-alanine, N-alkyltaurines such as the one prepared by reactingdodecylamine with sodium isethionate according to the teaching of US.Pat. No. 2,658,072, N-higher alkyl aspartic acids such as those producedaccording to the teaching of US. Pat. No. 2,438,091, and the productssold under the trade name Miranol and described in US. Pat. No.2,528,378.

Cationic synthetic detergents include those quaternary ammonium,quaternary phosphonium, and ternary sulfonium compounds containing asingle straight chain or branched aliphatic radical containing fromabout 6 to about 20 carbon atoms such as dodecyltrimethylammoniumchloride; nonylbenzylethyldimethylammonium nitrate; tetradecylpyridiniumbromide; octadecylbutylpropylmethylphosphonium nitrite;decyldimethylsulfonium chloride; etc.

Detergent formulations containing the antibacterial compositions of thepresent invention can also contain from about to about 90%, preferablyfrom about to about 90% of water-soluble alkaline detergency buildersalts, either of the organic or inorganic types. Examples of suchbuilder salts can be found in US. Pat. No. 3,336,233, issued Aug. 15,1967, column 9, lines 2966, which is incorporated herein by reference.However, at a very high pH, the compound may undergo alkaline hydrolysisand accordingly, for longterm stability, the detergent formulationsshould have a pH of less than about 10 and preferably the pH shouldbe'approximately neutral. The detergent formulations can also containany of the usual adjuvants, diluents, and additives, for example,perfumes, anti-tarnishing agents, anti-redeposition agents, dyes,fluorescers, suds builders, suds depressors and the like withoutdetracting from the advantageous properties of the antibacterialcompositions of the present invention.

Examples of diluents which may be incorporated into a syntheticdetergent bar in amounts of up to about 80% of the bar include soaps,especially alkaline earth metal insoluble soaps, (alkaline earth saltsof higher fatty acids); starches such as cornstarch; and clays such aschina clay or fullers earth. Other diluents include inorganic salts suchas sodium and potassium chlorides and sulfates. Such diluents add bulkto the bar and improve its cosmetic properties without impairingits'detergent or cohesive properties.

The antibacterial and antifungal efficac y of the phenylbismuthbis(2-pyridinethiol l-oxide) is disclosed in the following examples.

EXAMPLE I Preparation of Phenylbismuth bis(2-pyridinethiol l-oxide)164.7 grams of diphenylbismuth acetate (0.39 moles) were slurried in2,600 ml. of dimethylformamide. 59.7 grams of sodium 2-pyridinethioll-oxide (0. 39 mole, 97.3%) were dissolved in 1,300 ml. ofdimethylformamide and 18 g. of water were added to this solution. Thetwo solutions were then mixed while stirring at about 32C. The solutionturned yellow. The solution was continuously stirred for minutes, andthen put on a steam bath for 15 minutes where a temperature of 52C. wasattained. The solution was then put on a heating mantle forapproximately 1 hour at about 52 58C. The solution was then filtered,and the filtrate separated with dichloromethane and water (a ratio ofapproximately 121:2). The top layer which contained water anddimethylformamide was discarded. The bottom layer was filtered andwashed with water and ether. The resulting impure phenylbismuthbis(2-pyridinethiol l-oxide) was dried in vacuo.

Approximately 350 g. of this phenylbismuth bis(2- pyridinethiol l-oxide)was purified as follows: 30 g. of the crude material was dissolved in2,000 ml. dimethylacetamide at about 60C. The solution was stirred for'approximately 5 minutes, during which time the phenylbismuthbis(2-pyridinethiol l-oxide) was dissolved, leaving the impurities whichwere separated by filtering. The filtrate was then diluted with an equalvolume of water to precipitate out the phenylbismuth bis(2-pyridinethiol l-oxide). The mixture was cooled in an ice bath toprecipitate as much material as possible, and this'material was thenseparated by filtering. The

residue was washed with water and ether and dried in Calculated Found C35.7 35.535.3 H 2.4 2.3- 2.2 N 5.2 5.1 (Kjeldahl) Bi 38.8 39.0-39.1 S11.9 12.0-12.2

EXAMPLE II The phenylbismuth bis(Z-pyridinethiol l-oxide) preparedaccording to the process of Example I was tested for antibacterialefficacy in the following tests:

I. Minimal Inhibitory Concentration (MIC) in Agar 10,000 ppm. stocksolutions of phenylbismuth bis( 2- pyridinethiol l-oxide) were preparedin dimethylformamide (DMF). The active was diluted to the desired testconcentration and added to 19-20 ml. of molten trypticase soy agar (TSA)to give a series of graded concentrations (ppm). Thorough rotation ofplates assured adequate mixing of the sanitizer before agarsolidification. Appropriate control plates containing plain TSA wereincluded. All plates remained at room temperature overnight.

Trypticase soy broth cultures for each test organism (24 hour) werediluted in peptone water to give approximately cells per 0.01 ml. Theagar plates, marked in sectors, were inoculated by dropping one drop ofeach diluted culture from a Kline antigen microdropper onto theappropriate sector of agar. The drops were allowed to dry. The plateswere incubated 48 hours at 37C. and then examined for growth. Theweakest concentration which completely inhibited growth of an organismwas the MIC. The results for the tests were as follows:

Gram-Positive Organisms Staphylococcus aureus (S.a.) Staphylococcusepidermidis (S.ep.) Streptococcus faecalis (St.f.) Streptococcus sp.(St. 126) Sarcina Iuteu (Sar.l.) Diphlheroid sp. (Dip. l6)Brcvibaclerium ammoniagenes En'sipelolhrix insidiosu Lactabacillusleichmanni Bacillus suhtilus C lostridium perfringcns C orynebacteriumacnes Axilla diphtheroid No. 16 Oral Streptococcus N0. 126 Mycobacleriumphlei Mycobacterium smegmatis Mycobctclerium balmi Gram-NegativeOrganisms A 7-day old culture of Corynebac'terium acnes grownanaerobically on brain heart infusion agar plus 1% glucose (Bl-llA 1% G)was washed from the slant withml. of peptone water and drop inoculatedon plates containing varying concentrations of phenylbismuthbis(2pyridinethiol l-oxide) in BHlA 1% G. The MIC for this organism was5 ppm. A similar test was run using Pityrosporum ovale with TSA plus0.1% of a 95:5 ratio of oleic:palmitic acid as the culture medium. TheMIC was 5 ppm.

Fungistatic tests were performed using a modified gradient platetechnique reported by Hund and Sandham (Applied Microbiology 17 No.2:329-30, 1969). Results were as follows: Aspergillus niger 5.8 ppm;Microsporum gypseum 1 ppm.

11. Human Corneum Disc Diffusion Test Cornified epidermis was obtainedfrom the plantar surfaces of human volunteers by cutting sheets ofuniform thckness (0.4 mm.) with a dermatome. Discs, 6 mm. in diameter,were cut from the sheets with a No. 2 cork borer. A 1% solution ofphenylbismuth bis(2- pyridinethiol l-oxide) was prepared by dissolvingthe material in DMF to make a 10,000 ppm. stock solution and adding therequired amount of this solution to a 2.5% solution of pHisoderm (acommercially available skin cleansing detergent). Twenty ml. of the 1%solution of phenylbismuth bis(2-pyridinethiol l-oxide) in pHisoderm wasadded to a small screw-cap vial. A control vial was prepared containingml. of the pHisoderm solution alone. Six skin discs were added to eachof the vials which then were mechanically agitated for 10 minutes in a50C. water bath. The vial contents were transferred to a small beakerwhere the liquid was removed by suction, and the discs were rinsed threetimes with ml. of distilled water, each rinse followed by suctionremoval of the rinse water. The discs were then dried for 2 hours on apaper towel covered with a plexiglass shield to prevent aircontamination. The dry discs were placed on the surface of 15 m1. ofsolidified TSA in a Petri dish (one test disc and one control/dish). Al:l0,000 dilution of each of the six test organisms in TSA at 50C. wasprepared. Each Petri dish was overlaid with 10 ml. of agar seeded withoneof the organisms. After agar solidification, the dishes wererefrigerated overnight to allow diffusion of any sanitizer away from thedisc into the medium. The next day, the dishes were placed in a 37C.incubator for 24 hours. The diameter of any zone which was clear ofbacterial growth was measured in mm. These measurements included the 6mm. diameter disc. A clear zone is indicative of sanitizer retention onthe skin after the washing and rinsing process. The results were asfollows:

E.c. Psxzi. S.m. l\'.p. F..21.

II 6.5 I L5 13 9 No zones were produced around discs washed in thepHisoderm control solution.

111. Filter Disc Diffusion Test A test which was similar to the skindisc diffusion test was run using filter discs and several types offabric discs to give an indication of how much sanitizer would remainattached to paper and cloth after rinsing. The results were as follows:

1% phenylbismuth bis(2-pyridinethiol l-oxide) in pHisoderm was used by12 subjects who washed their hands 4 times. These subjects were chosenat random from a large group of available subjects who use nonsanitizerproducts exclusively for personal hygiene. The regimented washings inthe laboratory followed this procedure: The hands were moistened under100F. running tap water. The product was squeezed from a plastic bottleinto the palm; the amount approximated the size of a 25-cent piece. Theproduct was then distribut'ed over the hands and the lather was workedfor 90 seconds. The hands were then rinsed under running tap water for30 seconds. The four exposures were spread over 2 days, and on theafternoon of the second day, the subjects washed their hands 4 timesusing a blank bar soap containing no antibacterial agents. A fifthstandardized washing was then done in a basin containing 1 liter ofsterile distilled water with careful rinsing in this basin. Aliquotswere taken from the thoroughly mixed basin contents, added to 30 ml. ofsterile distilled water in a membrane funnel, and passed through sterilemembrane filters with vacuum suction. The filters were then incubated onpads saturated with 2X concentrated trypticase soy broth plus 10% horseserum and 1% Tween in plastic dishes for 48 hours at 37C. Coloniesappearing on the filters were counted and these numbers multiplied bythe appropriate dilution factor to determine the number ofbacteria/liter in the fifth basin contents. The numbers per basin foreach panelist were converted to logarithms to minimize unusually high orlow counts. These values were averaged to determine the mean log of thefifth basin bacterial count. Calculation of the log percent reductionfor 1 1 l 2 each subject was made using the log of 1.3 X 10 or 6.1 184.an average fifth basin bacterial count obtained from more than 500handwashings by non-antibacterial Composition No. 4 Percent soap users.These values were averaged to obtain the mean log percent reduction. Theresults were as fol- 5 Dimethyl coconut iin inc oxide 3,0 lows, Disodiumlauryl beta-iminodipropioiiatc 5.0 Sodium coconut sulfate 4.0 Coconut.dicthniiolnniide 1.0 Phenylbismuth bist Z-pyridincthiol l-oxide) l.()Log 71 Reduction Mcnn Log F vlor less than 0.0l 9539 478, I0 Citric acidto ad ust pH to 7.5

Water balance The iilkyl radical is derived from middle cut coconutalcohol and has A second handwashing test in which the subjects iiillfollowing chain length wmimilmn: 0.1 1.2M

t in used a measured amount of product (5 ml.) showed the *Wh lc cutfollowing result:

Composition 5 g A shampoo composition is obtained by uniformly LogReducllt" M611" Log mixing together the following ingredients:

Composition No. 5

These tests ShOW that hen lbismuth biS( 2- A sham oo composition isobtained bv uniforml mixin to ethcr the p y P f H t Y 2 g o owingir greicn s: pyn'dmethlol l 0X lde) m g vehlcle ls ff 47 tricthanolamine saltof the sulfated condensation product against normal Skln bacteria inVlVO Under OI'Id UO S of of 3 moles of ethylene oxide and 1 mole ofcoconut oil fatt 1 2 lhlh' thfll' h'l thd't'ht' 7 actua aco o aving e oowmgc am eng is n u ion: 1

C 66% C 2371 C and 971 C r... skin Disc Drop overlay Testiiiiia'iilzii'iiiiiiifirst?isnziriikisg'iib Skin discs of the type usedin the skin disc diffusion Slug??? gfk j g g ia gzt test were washed invarious concentrations Of phenyl- 371 monoethanolamide of coconut oilfatty acids having the bismuth bis(2-pyridinethiol l-oxide) in pHisodermto gagrg 5%? gg? f "g i l-h l'i 18' determine the minimum parts permillion of phenylbis- W. Phcnylbismuth bis(2-pyridinethiol l-oxide).

re d i hib' 371 dicthanolamide of coconut oil fatty acids having themuth lms(2 pyndmethlol oxide) qulr It following chain lengthdistribution: 16% C 48% C bacteria seeded and placed directly on thedisc. The 1 Cw 9%Cm, and 10% Cm values found were as follows: ethanol.

0.75% methyl cellulose a 2% solution of which has a viscosity of 4000cps. at 68 F. and a gel point of 140F. 0.7571 perfume. $.11. E.c. Ps.abalance, water.

4O Shampoo formulations containing phenylbismuth bis 2- ridinethioll-oxide are desirable since the As can be seen from the above date,phenylbismuth i gg dandruff y bis(2-pyridinethiol l-oxide) is aneffective antibacterial agent against a wide variety of microorganisms(baete- MPLE IV ria, yeasts, and fungi) and is substantive to skin,paper, I and cloth; Personal Use Detergent Lotion EXAMPLE 1]]Composition No. 6 Percent Potassium coconut glyceryl ether sulfo 3.0Shampoo Compositions nate (about 23% diglyceryl and the 5() balancesubstantially all monoglyceryl) Composition No. 1 No. 2 No. 3 Sodiumcoconut glyceryl ether sulfonate 4.0

(diglyceryl and monoglyceryl content 23 2 as above) P i fziny Sodiumtallow glyccryl ether sulfonate 3.0

alcohol sodium salt Sodium curate 87 8] (diglyceryl and monoglycerylcontent Sodium alkyl glyceryl & as above); the tallow zt lkyl radicalsether Sulfonmc, 5 5 correspond to those o substantially Sodium acylSarcosinmc-g i0 tallow alcohols containing approxiv mately 271 C 327: Cand 6071 C Sodium sulfate 0 8 0.8 2.6

. Coconut dimethylamine oxide 5.0 Sodium chloride 6.6 Trisodium hm hatel 2 1 Sodium salt of sulfated condensation 2.0 Diethanolufnidepof 2 0product of 1 mole of nonylphenol with 4 moles ethylene oxide coconutfatty acids P t m 3 h t l 0 Acetylated lanolin L0 1.0 L0 g pyn -f a t? dylbismuth bis(2-pyridinethiol l-oxide) 2.0 gg f W2 pyri {-8 Sodiumchloride (in addition to 3.0

n l i that from detergents) Sodium toluene sulfonate 2 5 wine 7 7 g l 74 Sodium carboxymethylcellulose 0.3 P" (degree of substitution0.65-0.95;

viscosity of 1% s0ln., 1000-2000 Alky'l radicals derived from fattyalcohol. 25.37: from coconut and 371 from at 250C.) mllow- Acrylamidepolymer (contains S-lO mole per- 0.l

-Acyl radicals derived from coconut fatty acids.

cent acrylic acid radicals; monomer is less than 0.05%; viscosity of a0.5% soln.

EXAMPLE lV-Continued -Continued Personal Use Detergent LotionComposition Percent Sodium siTEatc (SlO :Na O=2:l) 7,0 Composmo" N 6Percent 5 Phenylbismuth bis(2-pyridinethiol l-oxide) 3.0

ls about 5 at 25C) Water and minors balance to 100 Salts (sodium andpotassium chloride 1-2 and sulfate from detergents) water balance Thiscomposition, in addition to performing well in "Coconut indicates alkylradicals corrcsonding to those ol' niddlc cut coconut fatty itsClea-rung p yv lmparts conslderable antibacte alcohol containingapproximately 2% Cm. 667: C 239? C, and 9% CM i l i i to f b i l d i i li Substantially equivalent results are obtained, i.e., EXAMPLE V goodcleaning and good odor reducing properties, when the sodiumdodecylbenzene sulfonate of Example Cream Shampoo \/II is replaced, onan equal weight basis, by the followmg: Percent dodecyltrimethylammoniumchloride; Sodium coconut glyceryl ether 143nonylbenzylethyldlmethylarnmonium nitrate;

sulfonate (about 29% diglyceryl tetradecylpyrldrmum bromide; gfg g gg yf subsmmany octadecylbutylpropylmethylphosphonium nitrite; Sodium tallowglyceryl ether sulfonate 2.0 decyldlmethylslllfomum chlonde;

3 3 g y 'y the balance (hexylphenyl)dlmethylbenzylammomum fluoride; sustantia y monog ycery Sodium chloride 7 6'7elcosyldlmethylbenzylphosphonlum chloride, Sodium sulfate 3.5coconutalkylmethylmorphohnlum nitrate; N'laumylsarclsinale octadec lmethlbenz lsulfonium sulfate" Phenylbismuth bis(2-pyridinethiol l-oxide 2.025 1 l y M Middle-cut coconut diethanolamine O5 y py l l l c e,Acetylated lanolin L0 laurylpyrldmlum bromide; gf f' g' laurylpyridiniumbisulfate;

laurylpyridinium-5-chloro-2-mercaptobenzothiazole; o. 667: 6.2.2.3 u.and 9 7, Cm. laurylpicolinium-p-toluenesulfonate;

tetradecylpyridinium bromide;

l ri chl EXAMPLE v1 PY PF E cetylpyrldrmum bromide; A milled toiletdetergent bar is prepared m accorl li i li i b id dance with methodsknown and used in the art and havlaurylisoquinolinium saccharinate; inthe followin corn osition: alk liso uinolinium bromide; g g P y qN-cetyl-N-ethyl-morphol1n1um ethosulfate; benzalkonium chloride;Compmnm" Percent monoquaternaries R N X (one R group is fatty); Sodiumalkyl glycerol ether sulfonate 8.0 40 octadecyltrlmetbylammonrum c rl fyg p derivedfmm the l coconut alkyl trrmethylammonlum chloride;

by 03mm" dodecylbenzyltri( octyldecyl)ammonium chloride; Potassium alkylsulfate (alkyl group 20.0 monoquaternaries R N X (two R groups arefatty);

f fl f? g' gf f g dihexadecyldimethylammonium chloride; 1 l1 383L555; ofeoiomlt oil) y di-coconut alkyl dlmethylammomum chloride; Magnesium soapof 80:20 tallow: 1T0 monoquaternarles R N*X' (three R groups are coconutfatty acids fatt Inorganic salts (sodium and potassium 32.0 y achlorides and sulfates) trl(hydrogenated tallow) methylammomum chloride;Phenylbismuth bisO-pyridinethlol l-oxlde) l.0 distilled tallow amineacetate; water and minors balance to I00 diamine acetates 5O Middlecutalcohols huvinguchuin length distribution substuntiullyas follows: 271N-oleyl propylene dlamlne monoacetate; sodium tallow alkyl sulfate;

potassium coconut alkyl glyceryl ether sulfonate; Thls b W exhlblts goodQ reducmg sodium salt of randomly sulfonated paraffln containpropertiesevidencing antibacterial effectiveness. It reing an average of 152Carbon atoms. duces the number of bacteria on the skm significantly.ammonium trideicyl sulfate,

EXAMPLE V11 condensation product of octyl phenol with 15 moles ofethylene oxide per mole of octyl phenol; A granular built syntheticdetergent composltlon dimethyldodecylamine oxide; having the followingformulation can be prepared and dodecyldimethylphosphine Oxide; theantibacterial compositions of the present invention tetradecyl methylsulfoxide; can be mcorpmted therein3-(N,N-dimethyl-N-hexadecylammonio)propane-lsulfonate;3-dodecylaminopropionate; and Composition Percent dodecyl-B-alanine.

The invention has been described above in COZlJUl'lC- smllum L tion withtoilet and laundry detergents. It will be obvi- Sodlum trlpolyphosphate(M) I 40 ous to those skilled in the art, however, that the ant|- Sodiumsulfate bacterial compositions of the present invention can also bebeneficially employed in such products as shampoos, foot powders,antiseptic ointments, cosmetic products and the like.

A fabric softening composition having the following formulation can beprepared. The antibacterial and antifungal effectiveness of thephenylbismuth bis(2- pyridinethiol l-oxide) is especially desirablesince the antibacterial and antifungal compound is extremely substantiveto cloth.

Composition Percent Dialkyl dimethylammonium chloride 7 75% activeingredient dispersed in isopropanol and water, the dialkyl groups beingapproximately 24% hexadecyl, 75% octadecyl and 1% octadecenyl Thecondensation product of 30 3 moles of ethylene oxide with one mole ofcoconut alcohol Color and perfume 0.3 Phenylbismuth bis( Z-pyridinethioll-oxide) 1.0 Water balance Twenty ppm of PBDP were added to a 0.1%aqueous concentratiton of Downy, a commercial cationic softenercontaining a ditallowalkyl dimethylammonium chloride active. Thiscomposition, when used at 27C. for 10 minutes to treatDacron-prebrightened, Nylon, muslin, Nylon-prebrightened,muslin-prebrightened, and Dacron:cotton (65:35)-prebrightened clothwhich had been washed with Ivory Snow, a commercial soap powder, andmachine dried, completely controlled the growth of S. Aureus, S.faecalis, E. coli, C. albicans, and P. mirabilis. With similarcompositions containing 5 ppm. PBDP, one rinse gave complete protectionagainst S. aureus and S. faecalis, after three rinses E. coli and C.albicans are stopped, and after four rinses, P. mirabilis is inhibited.With similar compositions containing 30-40 ppm. PBDP, one rinse gaveprotection against P. aeruginosa on muslin, nylon, and the Dacron:cottnblend.

What is claimed is:

1. An antibacterial and antifungal detergent composition comprising:

A. a water-soluble detergent selected from the group consisting of soapsand non-soap synthetic detergents; and

B. from about 0.2 to about 3% of phenylbismuth bis(2-pyridinethioll-oxide);

said detergent composition having a pH of less than about l0.

2. The antibacterial and antifungal detergent composition of claim 1wherein the phenylbismuth bis(2- pyridinethiol l-oxide) is present in aconcentration of about 1.5%.

3. The antibacterial and antifungal composition of claim 1 in the formof a shampoo consisting essentially of:

A. a water-soluble detergent selected from the group consisting of soapsand non-soap synthetic detergents;

B. from about 0.2 to about 3% of phenylbismuth bis(2-pyridinethioll-oxide); and

C. balance, water and minors; said shampoo composition having a pH ofless than about 10.

4. The antibacterial and antifungal detergent composition of claim 1 inthe form of a synthetic antibacterial and antifungal detergent toiletbar consisting essentially of:

A. a water-soluble synthetic detergent;

B. diluents;

C. from about 0.2 to about 3% of phenylbismuth bis(2-pyridinethioll-oxide); and

D. balance, water and minors.

5. The antibacterial and antifungal detergent composition of claim 1 inthe formof an antibacterial and antifungal detergent soap bar consistingessentially of:

A. a metallic salt of a fatty acid of from about 10 to about 20 carbonatoms;

B. from about 0.2 to about 3% of phenylbismuth bis(2-pyridinethioll-oxide); and

C. balance, water and minors.

6. The antibacterial and antifungal composition of claim 1 containing asan additional ingredient a watersoluble, alkaline detergency buildersalt.

1. AN ANTIBACTERIAL AND ANTIFUNGAL DTERGENT COMPOSITION COMPRISING: A. A WATER-SOLUBLE DETERGENT SELECTED FROM THE GROUP CONSISTING OF SOAPS AND NON-SOAP SYNTHETIC DETERGENTS; AND B. FROM ABOUT 0.2 TO ABOUT 3% OF PHENYLBISMUTH BIS(2PYRIDINETHIOL 1 -OXIDE); SAID DETERGENT COMPOSITION HAVING A PH OF LESS THAN ABOUT
 10. 2. The antibacterial and antifungal detergent composition of claim 1 wherein the phenylbismuth bis(2-pyridinethiol 1-oxide) is present in a concentration of about 1.5%.
 3. The antibacterial and antifungal composition of claim 1 in the form of a shampoo consisting essentially of: A. a water-soluble detergent selected from the group consisting of soaps and non-soap synthetic detergents; B. from about 0.2 to about 3% of phenylbismuth bis(2-pyridinethiol 1-oxide); and C. balance, water and minors; said shampoo composition having a pH of less than about
 10. 4. The antibacterial and antifungal detergent composition of claim 1 in the form of a synthetic antibacterial and antifungal detergent toilet bar consisting essentially of: A. a water-soluble synthetic detergent; B. diluents; C. from about 0.2 to about 3% of phenylbismuth bis(2-pyridinethiol 1-oxide); and D. balance, water and minors.
 5. The antibacterial and antifungal detergent composition of claim 1 in the form of an antibacterial and antifungal detergent soap bar consisting essentially of: A. a metallic salt of a fatty acid of from about 10 to about 20 carbon atoms; B. from about 0.2 to about 3% of phenylbismuth bis(2-pyridinethiol 1-oxide); and C. balance, water and minors.
 6. The antibacterial and antifungal composition of claim 1 containing as an additional ingredient a water-soluble, alkaline detergency builder salt. 